In peptides, the β-turn is a subset of the reverse turn and is a common feature of biologically active peptides and proteins; it is widely thought to act as a molecular recognition site for many biological processes. Specific types of β-turns are classified according to their geometry.
The b-turn is defined as any tetrapeptide sequence with a 10-membered intramolecularly H-bonded ring, in which the Cai to Cai+3 distance varies from 4 to 7 Å. Depending on f2, y2, f3 and y3 there are many types of b-turn structures described in literature. (See: Gillespie et al., “Conformational Analysis of Dipeptide Mimetics”, Biopoly, Vol. 43, (1997), pp. 191-217; Venkatachalam, Biopolymers, Vol. 6, (1968), pp. 1425-36.
The subject invention compounds are mimetics for β-turn peptides. Such compounds are useful as probes for the study of molecular recognition events, including enzyme inhibition, cell-cell and cell-matrix interactions. One physical consequence of such conformational constraint of the subject compounds is a limiting of the number of accessible conformational states of the molecules, leading to a better definition of the bioactive conformation of corresponding active peptides.
Information regarding β-turn peptides and mimetic compounds can also be found, for example, in the following references: Ball et al., “β-Turn Topography”, Tetrahedron, Vol. 49, No. 17 (1993), pp. 3467-3478; Kahn, “Peptide Secondary Structure Mimetics: Recent Advances and Future Challenges”, SYNLETT, (November 1993), pp. 821-826; Hanessian et al., “Design and Synthesis of Conformationally Constrained Amino Acids as Versatile Scaffolds and Peptide Mimetics”, Tetrahedron, Vol. 53, No. 38 (1997), pp. 12789-12854.